Colorectal mucosal histamine release by mucosa oxygenation in comparison with other established clinical tests in patients with gastrointestinally mediated allergy

AIM： This study evaluated colorectal mucosal histamine release in response to blinded food challenge-positive and-negative food antigens as a new diagnostic procedure. METHODS： 19 patients suffering from gastrointestinally mediated allergy confirmed by blinded oral provocation were investigated on grounds of their case history, skin prick tests, serum IgE detection and colorectal mucosal histamine release by ex vivo mucosa oxygenation. Intact tissue particles were incubated/stimulated in an oxygenated culture with different food antigens for 30 min. Specimens challenged with anti-human immunoglobulin E and without any stimulus served as positive and negative controls, respectively. Mucosal histamine release （% of total biopsy histamine content） was considered successful （positive）, when the rate of histamine release from biopsies in response to antigens reached more than twice that of the spontaneous release. Histamine measurement was performed by radioimmunoassay. RESULTS： The median （range） of spontaneous histamine release from colorectal mucosa was found to be 3.2 （0.1%-25.8%） of the total biopsy histamine content. Food antigens tolerated by oral provocation did not elicit mast cell degranulation 3.4 （0.4%-20.7%, P=0.4）, while anti-IgE and causative food allergens induced a significant histamine release of 5.4 （1.1%-25.6%, P = 0.04） and 8.1 （1.5%-57.9%, P = 0.008）, respectively. 12 of 19 patients （63.1%） showed positive colorectal mucosal histamine release in accordance with the blinded oral challenge responding to the same antigen （s）, while the specificity of the functional histamine release to accurately recognise tolerated foodstuffs was found to be 78.6%. In comparison with the outcome of blinded food challenge tests, sensitivity and specificity of history （30.8% and 57.1%）, skin tests （47.4% and 78.6%） or antigen-specific serum IgE determinations （57.9% and 50%） were found to be of lower diagnostic accuracy in gastrointestinally mediated allergy. CONCLUSION： Functional testing of the reactivity of colorectal mucosa upon antigenic stimulation in patients with gastrointestinally mediated allergy is of higher diagnostic efficacy.

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes.Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation.A large number of studies have shown that autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal(GI)cells.However,the role of autophagy in GI diseases remains controversial.This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases,in order to provide new ideas for their diagnosis and treatment.

Primary gastroduodenal tuberculosis presenting as gastric outlet obstruction:A case report and review of literature

BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous illness.This disease is prevalent in low-income countries,posing a significant global health challenge.Gastrointestinal TB is one of the three forms.The disease can mimic other intra-abdominal conditions,leading to delayed diagnosis owing to the absence of specific symptoms.While gastric outlet obs-truction(GOO)remains a frequent complication,its incidence has declined with the advent of proton pump inhibitors and Helicobacter pylori eradication therapy.Gastroduodenal TB can cause upper gastrointestinal hemorrhage,obstruction,and malignancy-like tumors.CASE SUMMARY A 23-year-old male presented with recurrent epigastric pain,distension,nausea,vomiting,and weight loss,prompting a referral to a gastroenterologist clinic.Endoscopic examination revealed distorted gastric mucosa and signs of chronic inflammation.However,treatment was interrupted,possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or diabetes.Subsequent surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal wall.Resection revealed gastric wall effacement with TB.CONCLUSION Primary gastric TB is rare,frequently leading to GOO.Given its rarity,suspicions should be promptly raised when encountering relevant symptoms,often requiring surgical intervention for diagnosis and treatment.

Clinical characteristics of acute non-varicose upper gastrointestinal bleeding and the effect of endoscopic hemostasis

BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distinguished by its abrupt onset,swift progression,and notably elevated mortality rate.AIM To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic hemostasis.METHODS We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023,utilizing our medical record system.Data pertaining to general patient information,etiological factors,disease outcomes,and other relevant variables were meticulously collected and analyzed.RESULTS Among the 532 patients diagnosed with ANVUGIB,the male-to-female ratio was 2.91:1,with a higher prevalence among males.Notably,43.6%of patients presented with black stool as their primary complaint,while 27.4%had hematemesis as their initial symptom.Upon admission,17%of patients exhibited both hematemesis and black stool,while most ANVUGIB patients primarily complained of overt gastrointestinal bleeding.Urgent routine blood examinations at admission revealed that 75.8%of patients had anemia,with 63.4%experiencing moderate to severe anemia,and 1.5%having extremely severe anemia(hemoglobin<30 g/L).With regard to etiology,53.2%of patients experienced bleeding without a definitive trigger,24.2%had a history of using gastric mucosa-irritating medications,24.2%developed bleeding after alcohol consumption,2.8%attributed it to improper diet,1.7%to emotional excitement,and 2.3%to fatigue preceding the bleeding episode.Drug-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals,while bleeding due to alcohol consumption showed the opposite trend.Additionally,diet-related bleeding was more common among the young age group compared to the middle-aged group.Gastrointestinal endoscopy identified peptic ulcers as the most frequent cause of ANVUGIB(73.3%),followed by gastrointestinal malignancies(10.9%),acute gastric mucous lesions(9.8%),and androgenic upper gastrointestinal bleeding(1.5%)among inpatients with ANVUGIB.Of the 532 patients with gastrointestinal bleeding,68 underwent endoscopic hemostasis,resulting in an endoscopic treatment rate of 12.8%,with a high immediate hemostasis success rate of 94.1%.

Gastric cancer secreted miR 214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells

Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell death.Apatinib is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis pathway.However,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported yet.Tumor.secreted exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been discovered.Here,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of Apatinib.In conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.

New trends in diagnosis and management of gallbladder carcinoma

Gallbladder(GB)carcinoma,although relatively rare,is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis.It is closely associated with cholelithiasis and long-standing large(>3 cm)gallstones in up to 90%of cases.The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes,GB wall calcification(porcelain)or mainly mucosal microcalcifications,and GB polyps≥1 cm in size.Diagnosis is made by ultrasound,computed tomography(CT),and,more precisely,magnetic resonance imaging(MRI).Preoperative staging is of great importance in decisionmaking regarding therapeutic management.Preoperative staging is based on MRI findings,the leading technique for liver metastasis imaging,enhanced three-phase CT angiography,or magnetic resonance angiography for major vessel assessment.It is also necessary to use positron emission tomography(PET)-CT or ^(18)F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake.Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6%of cases.Multimodality treatment is needed,including surgical resection,targeted therapy by biological agents according to molecular testing gene mapping,chemotherapy,radiation therapy,and immunotherapy.It is of great importance to understand the updated guidelines and current treatment options.The extent of surgical intervention depends on the disease stage,ranging from simple cholecystectomy(T1a)to extended resections and including extended cholecystectomy(T1b),with wide lymph node resection in every case or IV-V segmentectomy(T2),hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y,and adjacent organ resection if necessary(T3).Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery,but much attention must be paid to avoiding injuries.In addition to surgery,novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy(neoadjuvant-adjuvant capecitabine,cisplatin,gemcitabine)have yielded promising results even in inoperable cases calling for palliation(T4).Thus,individualized treatment must be applied.

A Meta-Analysis of the Prognostic and Clinicopathological Significance of circZFR in Human Gastrointestinal Cancers

Background: Studies of gastrointestinal (GIT) cancers have shown that circZFR could be involved in the development and progression of various GIT cancers. However, small sample sizes limit the clinical significance of these studies. Here, a meta-analysis was conducted to ascertain the actual involvement of circZFR in the development and prognosis of GIT cancers. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched up to December 31, 2023. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to evaluate the association between circZFR expression and overall survival (OS). Publication bias was measured using the funnel plot and Egger’s test. Results: 10 studies having 659 participants were enrolled for meta-analysis. High circZFR expression was associated with poor OS (HR = 1.4, 95% CI: 1.20, 1.70). High circZFR expression also predicted larger tumor size (OR = 4.38, 95% CI 2.65, 7.25), advanced clinical stage (OR = 5.33, 95% CI 3.10, 9.16), and tendency for distant metastasis (OR = 2.89, 95% CI: 1.62, 5.11), but was not related to age, gender, and histological grade. Conclusions: In summary, high circZFR expression was associated with poor OS, larger tumor size, advanced stage cancer and tendency for distant metastasis. These findings suggested that circZFR could be a prognostic marker for GIT cancers.

Two different mutational types of familial gastrointestinal stromal tumors:Two case reports

BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases/million each year.The rarer familial GISTs,which often represent a population,differ in screening,diagnosis,and treatment.Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs.However,whether the same genetic family has different phenotypes has not been reported.CASE SUMMARY We report two cases of rare GISTs in the same family:A male patient with the V561D mutation in exon 12 of the PDGFRA gene,who has been taking the targeted drug imatinib since undergoing surgery,and a female patient diagnosed with wild-type GIST,who has been taking imatinib for 3 years since undergoing surgery.The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy,and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease.CONCLUSION Different mutation types of familial GISTs in the same family are very rare,thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.

Advancements in hemostatic strategies for managing upper gastrointestinal bleeding: A comprehensive review

Upper gastrointestinal(GI)hemorrhage presents a substantial clinical challenge.Initial management typically involves resuscitation and endoscopy within 24 h,although the benefit of very early endoscopy(<12 h)for high-risk patients is debated.Treatment goals include stopping acute bleeding,preventing rebleeding,and using a multimodal approach encompassing endoscopic,pharmacological,angiographic,and surgical methods.Pharmacological agents such as vasopressin,prostaglandins,and proton pump inhibitors are effective,but the increase in antithrombotic use has increased GI bleeding morbidity.Endoscopic hemostasis,particularly for nonvariceal bleeding,employs techniques such as electrocoagu-lation and heater probes,with concerns over tissue injury from monopolar electrocoagulation.Novel methods such as Hemospray and Endoclot show promise in creating mechanical tamponades but have limitations.Currently,the first-line therapy includes thermal probes and hemoclips,with over-the-scope clips emerging for larger ulcer bleeding.The gold probe,combining bipolar electrocoagulation and injection,offers targeted coagulation but has faced device-related issues.Future advancements involve combining techniques and improving endoscopic imaging,with studies exploring combined approaches showing promise.Ongoing research is crucial for developing standardized and effective hemorrhage management strategies.

Importance of risk assessment,endoscopic hemostasis,and recent advancements in the management of acute non-variceal upper gastrointestinal bleeding

Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)is a common medical emergency in clinical practice.While the incidence has significantly reduced,the mortality rates have not undergone a similar reduction in the last few decades,thus presenting a significant challenge.This editorial outlines the key causes and risk factors of ANVUGIB and explores the current standards and recent updates in risk assessment scoring systems for predicting mortality and endoscopic treatments for achieving hemostasis.Since ANUVGIB predominantly affects the elderly population,the impact of comorbidities may be responsible for the poor outcomes.A thorough drug history is important due to the increasing use of antiplatelet agents and anticoagulants in the elderly.Early risk stratification plays a crucial role in deciding the line of management and predicting mortality.Emerging scoring systems such as the ABC(age,blood tests,co-morbidities)score show promise in predicting mortality and guiding clinical decisions.While conventional endoscopic therapies remain cornerstone approaches,novel techniques like hemostatic powders and over-the-scope clips offer promising alternatives,particularly in cases refractory to traditional modalities.By integrating validated scoring systems and leveraging novel therapeutic modalities,clinicians can enhance patient care and mitigate the substantial morbidity and mortality associated with ANVUGIB.

A systematic scoping review of study methodology for randomized controlled trials investigating probiotics in athletic and physically active populations

Background:The purported ergogenic and health effects of probiotics have been a topic of great intrigue among researchers,practitioners,and the lay public alike.There has also been an increased research focus within the realm of sports science and exercise medicine on the athletic gut microbiota.However,compared to other ergogenic aids and dietary supplements,probiotics present unique study challenges.The objectives of this systematic scoping review were to identify and characterize study methodologies of randomized controlled trials investigating supplementation with probiotics in athletes and physically active individuals.Methods:Four databases(MEDLINE,CINAHL,Cochrane CENTRAL,and Cochrane Database of Systematic Reviews)were searched for randomized controlled studies involving healthy athletes or physically active individuals.An intervention with probiotics and inclusion of a control and/or placebo group were essential.Only peer-reviewed articles in English were considered,and there were no date restrictions.Results were extracted and presented in tabular form to detail study protocols,characteristics,and outcomes.Bias in randomized controlled trials was determined with the RoB 2.0 tool.Results:A total of 45 studies were included in the review,with 35 using a parallel group design and 10 using a cross-over design.Approximately half the studies used a single probiotic and the other half a multi-strain preparation.The probiotic dose ranged from 2×10^(8)to 1×10^(11)colony forming units daily,and the length of intervention was between 7 and 150 days.Fewer than half the studies directly assessed gastrointestinal symptoms,gut permeability,or the gut microbiota.The sex ratio of participants was heavily weighted toward males,and only 3 studies exclusively investigated females.Low-level adverse events were reported in only 2 studies,although the methodology of reporting varied widely.The risk of bias was generally low,although details on randomization were lacking in some studies.Conclusion:There is a substantial body of research on the effects of prob iotic supplementation in healthy athletes and physically active individuals.Considerable heterogeneity in probiotic selection and dosage as well as outcome measures has made clinical and mechanistic interpretation challenging for both health care practitioners and researchers.Attention to issues of randomization of participants,treatments and interventions,selection of outcomes,demographics,and reporting of adverse events will facilitate more trustworthy interpretation of probiotic study results and inform evidence-based guidelines.

Reducing the global cancer burden with gastrointestinal screening: China's 30 years practice

Gastrointestinal(GI) cancers include esophageal [EC(International Classification of Disease 10^(th) revision: C15)], gastric [GC(C16)], and colorectal [CRC(C18-C21)] cancers. China is a high-incidence country of GI cancers.

Pancreatic giant malignancy simulating a gastrointestinal stromal tumor

Pancreatic acinar cell carcinoma(PACC)is a rare malignant tumor of pancreatic epithelial cells,which produces pancreatic exocrine enzymes.PACC originates from acinar cells and terminal branches of the pancreatic ducts in the exocrine tissue of the pancreas.PACC accounts for 1%−2%of pancreatic exocrine tumors[1].Herein,we present an elderly woman with PACC who recovered after effective laparoscopic surgery.The tumor was located on the left side of the abdomen;imaging suggested that it was a gastrointestinal stromal tumor of the gastric wall origin,infiltrating the tail of the pancreas and omentum,while postoperative pathology suggested PACC.

Utilization of pH-driven methods to fortify nanoemulsions with multiple polyphenols

Simple but effective methods are required to incorporate multiple bioactive polyphenols into delivery systems to increase their dispersibility,stability and bioavailability.We developed and tested three p Hdriven protocols for creating nanoemulsions loaded with multiple lipophilic polyphenols.These protocols differed in how the different polyphenols were incorporated into the nanoemulsions.The impact of these three methods on the formation,properties,and gastrointestinal fate of nanoemulsions loaded with curcumin,resveratrol,and quercetin was investigated.The three methods produced nanoemulsions with similar initial particle properties:droplet diameters(0.15,0.16,and 0.15μm)and zeta-potentials(–59,–58,and–58 m V),respectively.However,the average encapsulation efficiencies(82%,88%,and 61%),gastrointestinal stabilities(83%,97%,and 29%)and bioaccessibilities(77%,90%,and 73%)for curcumin,resveratrol,and quercetin were somewhat different.In particular,more quercetin degradation occurred using the approach that held it under alkaline conditions for extended periods.In general,the p H-driven method provides researchers with a versatile approach of incorporating multiple polyphenols with different characteristics into functional food and beverages using a simple and inexpensive method.

Implementation of gastrointestinal function protection in severe acute pancreatitis

Severe acute pancreatitis(SAP)is a serious systemic disease associated with strong local inflammatory reactions and serious systemic pathophysiological disorders caused by trypsin spillover.Patients with SAP are prone to exhibit gastrointestinal dysfunction.Meanwhile,gastrointestinal dysfunction further aggravates the systemic inflammatory response and metabolic abnormalities,resulting in a more critical condition of SAP.Gastrointestinal dysfunction is considered to be the“trigger”of multiple organ dysfunction syndrome[1].Thus,it is important to maintain gastrointestinal homeostasis in the treatment of SAP.

Effect of simulated gastrointestinal digestion on antioxidant,and anti-inflammatory activities of bioactive peptides generated in sausages fermented with Staphylococcus simulans QB7

Dry-fermented sausages are a good source of bioactive peptides,whose stability against gastrointestinal(GI)digestion determines their bioaccessibility.This study focused on evaluating the effect of peptide extracts from sausages fermented with Staphylococcus simulans QB7 during in vitro simulated GI digestion,including peptide profiles and antioxidant and anti-inflammatory activities.Peptides present in sausages were degraded during digestion,with molecular weight reduced from>12 kDa to<1.5 kDa.Besides,the content of amino acids increased from 381.15 to 527.07 mg/g,especially tyrosine being found only after GI digestion.The anti-inflammatory activities were increased after GI digestion,however,the changes in antioxidant activities were the opposite.A total number of 255,252 and 386 peptide sequences were identified in undigested,peptic-digested and GI-digested samples,respectively.PeptideRanker,BIOPEP-UWM and admetSAR were used to further predict the functional properties and intestinal absorption of the identified peptide sequences from GI digestion.Finally,18 peptides were discovered to possess either antioxidant or anti-inflammatory capacities.

Enteric neuropathy in diabetes:Implications for gastrointestinal function

Diabetes,commonly known for its metabolic effects,also critically affects the enteric nervous system(ENS),which is essential in regulating gastrointestinal(GI)motility,secretion,and absorption.The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions,such as gastroparesis and irregular bowel habits,primarily due to disruptions in the function of neuronal and glial cells within the ENS,as well as oxidative stress and inflammation.This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients.Additionally,it discusses the latest advances in diagnostic approaches,emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals.The editorial also reviews current and emerging therapeutic strategies,focusing on pharmacological treatments,dietary management,and potential neuromodulatory interventions.Ultimately,this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes,aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.

Clinical issues and challenges in imaging of gastrointestinal diseases:A minireview and our experience

Imaging techniques play a crucial role in the modern era of medicine,particularly in gastroenterology.Nowadays,various non-invasive and invasive imaging modalities are being routinely employed to evaluate different gastrointestinal(GI)diseases.However,many instrumental as well as clinical issues are arising in the area of modern GI imaging.This minireview article aims to briefly overview the clinical issues and challenges encountered in imaging GI diseases while highlighting our experience in the field.We also summarize the advances in clinically available diagnostic methods for evaluating different diseases of the GI tract and demonstrate our experience in the area.In conclusion,almost all imaging techniques used in imaging GI diseases can also raise many challenges that necessitate careful consideration and profound expertise in this field.

Cronkhite-Canada syndrome with esophagus involvement and sixyear follow-up:A case report

BACKGROUND Cronkhite-Canada syndrome(CCS)is a rare,noninherited disease characterized by gastrointestinal polyposis with diarrhea and ectodermal abnormalities.CCS polyps are distributed through the whole digestive tract,and they are common in the stomach and colon but very uncommon in the esophagus.CASE SUMMARY Here,we present a case of a 63-year-old man with skin hyperpigmentation accompanied by diarrhea,alopecia,and loss of his fingernails.Laboratory data indicated anemia,hypoalbuminemia,hypocalcemia,hypokalemia,and positive fecal occult blood.Endoscopy showed numerous polyps scattered throughout the digestive tract,including the esophagus.He was treated with nutritional support and glucocorticoids with remission of his symptoms.CONCLUSION Comprehensive treatment led by hormonal therapy can result in partial or full remission of clinical symptoms.Treatment should be individualized for each patient according to their therapy response.Surveillance endoscopy is necessary for assessing mucosal disease activity and detecting malignant transformation.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.